Impact of anti-VEGF treatment for diabetic macular oedema on progression to proliferative diabetic retinopathy: data-driven insights from a multicentre study.

Objective: To report insights on proliferative diabetic retinopathy (PDR) risk modification with repeated antivascular endothelial growth factor (VEGF) injections for the treatment of diabetic macular oedema (DMO) in routine care.

Methods And Analysis: Multicentre study (27 UK-National Health Service centres) of patients with non-PDR (NPDR) and DMO. Primary outcome was PDR development.

The British-Israeli Project for Algorithm-Based Management of Age-Related Macular Degeneration: Deep Learning Integration for Real-World Data Management and Analysis.

Introduction: The aim of this study was to describe the development of an integrative dataset, combining clinical and optical coherence tomography (OCT) imaging data by applying a deep learning (DL) algorithm for automated, objective, and comprehensive quantification of OCT scans in two large real-world datasets of eyes with neovascular age-related macular degeneration (nAMD). We further report baseline characteristics of the study population, focusing on demographics, clinical parameters, and quantitative retinal morphological features.

Methods: This retrospective study analyzed data from 5,207 eyes of 4,265 nAMD patients treated at two centers in the UK and Israel.

Effect of Faricimab versus Aflibercept on Hyperreflective Foci in Patients with Diabetic Macular Edema from the YOSEMITE/RHINE Trials.

Purpose: To compare the effect of faricimab, a dual angiopoietin-2 (Ang-2) and VEGF-A inhibitor, with aflibercept on resolution of hyperreflective foci (HRF) in patients with diabetic macular edema (DME).

Design: A post hoc analysis of the randomized, double-masked, noninferiority YOSEMITE/RHINE (NCT03622580/NCT03622593) phase III trials.

Participants: Adults with vision loss due to center-involving DME.

Onset of End-Stage Atrophic Age-Related Macular Degeneration as an End Point-A Delphi Study: Classification of Atrophy Meetings Report 7.

Purpose: To investigate whether consensus can be reached on the acceptability of end-stage atrophy onset as a clinical end point in early intervention trials of age-related macular degeneration (AMD), and the criteria for defining such an end point.

Design: A modified Delphi study.

Participants: International panel of experts in AMD, retinal imaging, and histopathology that are part of the Classification of Atrophy Meetings group.

Geographic atrophy: Understanding the relationship between structure and function.

Purpose: This review explores the complex relationship between anatomical alterations and functional consequences in geographic atrophy (GA), the advanced non-neovascular form of age-related macular degeneration. We examine the natural history, progression patterns, structural biomarkers, functional assessments, and structure-function correlations in GA.

Methods: Experts contributed specialized knowledge on GA pathophysiology, imaging biomarkers, and functional assessment methods.

Aflibercept With vs Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: A Randomized Clinical Trial.

Importance: The potential benefit of adding photodynamic therapy (PDT) to intravitreal aflibercept injection (IAI) in eyes with polypoidal choroidal vasculopathy (PCV) remains unclear.

Objective: To compare the functional and anatomical benefit of combination therapy using reduced-fluence PDT (RF-PDT) plus IAI vs IAI monotherapy in participants with PCV.

Design, Setting, And Participants: This double-masked, sham-controlled, randomized clinical trial was conducted at 2 centers in Singapore from January 2021 to June 2024 for participants aged 50 years or older with symptomatic macular PCV confirmed on indocyanine green angiography.

Dissecting the biological complexity of age-related macular degeneration: Is it one disease, multiple separate diseases, or a spectrum?

Clinicians recognize the heterogeneity of age-related macular degeneration (AMD) in presentation, progression, and treatment response, as well as the challenges in distinguishing it from other macular degenerations. As part of the 2024 Ryan Initiative for Macular Research meeting, a group of clinician-scientists and basic scientists were convened to consider the question of whether AMD should be classified as a single disorder or a spectrum of conditions. To answer this question, we reviewed research on several "dimensions" that constitute AMD risk or pathogenesis: genetics, ancestry, retinal imaging findings, diet and environment, aging, and outer retinal molecular and cellular pathways.

Visual Function Benefit After Treatment With Pegcetacoplan: Microperimetry Analysis From the Phase 3 Oaks Trial.

Purpose: To evaluate the impact of pegcetacoplan on its ability to slow the loss of visual function using microperimetry endpoints in eyes with geographic atrophy secondary to age-related macular degeneration (AMD).

Design: Post hoc analysis of phase 3 randomized controlled trial data.

Methods: Utilizing data from the OAKS study, which evaluated pegcetacoplan monthly (PM) or every other month (PEOM) vs sham for the treatment of GA secondary to AMD, microperimetry endpoints were assessed at baseline and every 6 months until 24 months, using a 10-2 grid composed of 68 points with a 4-2 threshold strategy.

Agreement Between Color, Fluorescein Angiography, and Spectral Domain Optical Coherence Tomography in the Detection of Macular Fibrosis in Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the agreement between fibrosis on color imaging-, fluorescein angiography (FA)-, and spectral domain optical coherence tomography (SD-OCT)-detected hyperreflective material (HRM) and assess their clinical relevance.

Design: Clinical cohort and diagnostic accuracy study.

Methods: Multimodal fundus images (color, FA, and SD-OCT) of 130 eyes with neovascular age-related macular degeneration, collected 18 months after the initiation of anti-vascular endothelial growth factor treatment (anti-VEGF) as part of the Early Detection of Neovascular AMD (EDNA) study, were regraded for fibrosis and HRM.

Visual Acuity Outcomes and Influencing Factors in a Cohort of UK Real-World Diabetic Macular Oedema Patients During the First Two Years of Anti-VEGF Treatment.

Background/objectives: The visual acuity (VA) outcomes after the first and second years of anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with diabetic macular oedema (DMO) were evaluated, and the factors associated with treatment success were investigated.

Methods: Using Medisoft electronic medical records (UK), this retrospective cohort study analysed VA outcomes, changes, and determinants in DMO patients at year 1 and year 2 after initial anti-VEGF injection. Descriptive analysis examined baseline demographics and clinical characteristics, while regression models were used to assess associations between these factors and changes in VA.

Lipid-lowering drug and complement factor H genotyping-personalized treatment strategy for age-related macular degeneration.

We investigated whether the effect of lipid-lowering drugs (LLDs) on age-related macular degeneration (AMD) differs according to the main complement genetic variants in Singapore Epidemiology of Eye Diseases (SEED) ( = 5,579) and UK Biobank studies ( = 445,727). The effect of LLD was determined for each stratum of 20 complement genetic variants. In SEED, 484 individuals developed AMD and 216 showed progression over 6 years.

Interplay between Lipids and Complement Proteins-How Multiomics Data Integration Can Help Unravel Age-related Macular Degeneration Pathophysiology: A Proof-of-concept Study.

Objective: Our objectives were to identify correlation patterns between complement and lipid pathways using a multiomics data integration approach and to determine how these interconnections affect age-related macular degeneration (AMD).

Design: Nested case-control study.

Subjects And Controls: The analyses were performed in a subset of the Singapore Indian Eye Study.

Visual Loss in Geographic Atrophy: Learnings from the Lampalizumab Trials.

Purpose: To assess the correlation of lesion growth rate and baseline factors, including foveal involvement and focality, on visual loss as measured by best-corrected visual acuity (BCVA) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Design: Retrospective analysis of the lampalizumab phase 3 (NCT02247479 and NCT02247531) and prospective observational (NCT02479386) trials.

Participants: Patients with bilateral GA.

Retinal Fluid and Thickness Fluctuations in Archway Trial for Port Delivery System with Ranibizumab versus Monthly Ranibizumab Injections.

Purpose: To determine proportion of eyes with neovascular age-related macular degeneration (nAMD) with retinal fluid and central subfield thickness (CST) fluctuations and evaluate their impact on best-corrected visual acuity (BCVA) in eyes treated with the Port Delivery System with ranibizumab (PDS) versus monthly intravitreal ranibizumab injections.

Design: Post hoc analyses of phase 3 Archway trial (NCT03677934).

Participants: Adults with nAMD responsive to anti-VEGF therapy.

Informing Endpoints for Clinical Trials of Geographic Atrophy.

Geographic atrophy (GA), the non-neovascular advanced form of age-related macular degeneration, remains an important disease area in which treatment needs are currently unmet. Recent clinical trials using drugs that target the complement pathway have shown modest yet consistent reductions in GA expansion but without commensurate changes in measures of visual function. In this review, we summarize information from the wide range of studies describing the characteristics of GA morphology and enumerate the factors influencing the growth rates of lesions and the directionality of expansion.

Macular neovascularization.

Neovascularization of the macula, a common complication of many chorioretinal diseases such as neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and pathologic myopia, results from increased synthesis of vascular endothelial growth factor (VEGF) by the retinal pigment epithelium and/or Müller cells because of localized ischemia and inflammation. The Consensus on Neovascular AMD Nomenclature (CONAN) study group acknowledged that these vessels may originate from either the choriocapillaris or the retinal microvasculature, prompting them to propose the term 'macular neovascularization' (MNV) to include intraretinal, subretinal, and sub-pigment epithelial neovascularization localized to the macula. MNV frequently appears as a grey-green macular lesion with overlying intraretinal thickening and/or subretinal exudation, causing metamorphopsia, reduced central vision, relative central scotoma, decreased reading speed, and problems with color recognition.

Fibrosis in age-related neovascular macular degeneration in the anti-VEGF era.

The natural history of neovascular age-related macular degeneration (nAMD) leads to scarring and loss of vision. Since the advent of anti-VEGF therapies, which are very effective for controlling exudation, large disciform scars are rarely encountered in the clinic. However long term studies show that smaller and less severe fibrotic scars are not uncommon and develop over time despite optimal treatment.

Topographic Clinical Insights From Deep Learning-Based Geographic Atrophy Progression Prediction.

Purpose: To explore the contributions of fundus autofluorescence (FAF) topographic imaging features to the performance of convolutional neural network-based deep learning (DL) algorithms in predicting geographic atrophy (GA) growth rate.

Methods: Retrospective study with data from study eyes from three clinical trials (NCT02247479, NCT02247531, NCT02479386) in GA. The algorithm was initially trained with full FAF images, and its performance was considered benchmark.

Contributions of Lipid-Related Metabolites and Complement Proteins to Early and Intermediate Age-Related Macular Degeneration.

Objective: Our objective was to determine the effects of lipids and complement proteins on early and intermediate age-related macular degeneration (AMD) stages using machine learning models by integrating metabolomics and proteomic data.

Design: Nested case-control study.

Subjects And Controls: The analyses were performed in a subset of the Singapore Indian Chinese Cohort (SICC) Eye Study.

Stereotactic radiotherapy for neovascular age-related macular degeneration (STAR): a pivotal, randomised, double-masked, sham-controlled device trial.

Background: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness. The first-line therapy is anti-vascular endothelial growth factor (anti-VEGF) agents delivered by intravitreal injection. Ionising radiation mitigates key pathogenic processes underlying nAMD, and therefore has therapeutic potential.